Urologists have long been searching for an alloplastic or biodegradable material suitable for use as a urinary bladder replacement graft. Many experiments have been conducted utilizing synthetic biomaterials such as silicone rubber, polytetrafluoroethylene and polypropylene for bladder reconstruction. Such materials have been found generally to induce foreign body-type reactions resulting in the rejection or mineralization of the graft.
The reported failures of experiments with synthetic biomaterials, have led researchers to investigate the use of natural or synthetic biodegradable materials, such as gastrointestinal, placental, amniotic and pericardial tissues and synthetic resorbable polymers, for bladder regeneration. These materials serve as a scaffold for endogenous cell growth, but dissolve prior to the onset of any foreign body-type reactions. In particular gastrointestinal tissue has been a preferred source of material for bladder reconstruction. However, the use of gastrointestinal tissue in bladder reconstruction has been associated with deleterious side effects such as infection, intestinal obstruction, mucus production, electrolyte abnormalities and carcinogenicity.
Placental, amniotic and pericardial tissue grafts are useful as graft materials for replacing urinary bladder tissue however, such graft materials suffer the disadvantage of graft shrinkage, and they fail to promote complete bladder wall regeneration (tissue having a urine impermeable layer and a functional muscle cell layer).
Clearly a tissue graft material is desired which is non-immunogenic, which is not subject to gross shrinkage after implantation, and which promotes the growth of endogenous urinary bladder tissues having a urine impermeable cell layer and a functional muscle cell layer.
The present invention is directed to the use of vertebrate submucosa matrices for promoting the replacement of damaged or diseased portions of a urinary bladder with endogenous urinary bladder tissue. The collagenous submucosa tissue used in accordance with the present invention comprise highly conserved collagens, glycoproteins, proteoglycans, and glycosaminoglycans in their natural configuration and natural concentration. Submucosal tissue can be obtained from various sources, including particularly intestinal tissue harvested from animals raised for meat production, including, for example, pigs, cattle and sheep or other warm-blooded vertebrates. This tissue can be used in either its natural configuration or in a comminuted or partially digested fluidized form. Vertebrate submucosal tissue is a plentiful by-product of commercial meat production operations and is thus a low cost tissue graft material, especially when the submucosal tissue is used in its native sheet configuration.
It is known that compositions comprising the tunica submucosa and the basilar portions of the tunica mucosa of the intestine of warm-blooded vertebrates can be used as tissue graft materials in sheet form. See U.S. Pat. No. 4,902,508. The compositions described and claimed in that patent are characterized by excellent mechanical properties, including high compliance, a high burst pressure point, and an effective porosity index which allowed such compositions to be used beneficially for vascular graft constructs. The graft materials disclosed in that patent are also useful in tendon, ligament and other connective tissue replacement applications. When used in such applications the preferred graft constructs appear to serve as a matrix for the regrowth of the tissues replaced by the graft constructs. Intestinal submucosal tissue has undergone extensive immunologic testing in over 600 cross-species implants and has never been shown to elucidate a rejection reaction.
Furthermore, it is known that intestinal submucosa can be fluidized by comminuting and/or protease digestion, without loss of its apparent biotropic properties, for use in less invasive methods of administration (e.g., injection or topical) to host tissues in need of repair. See U.S. Pat. No. 5,275,826. Fluidized comminuted intestinal tissue comprising tunica submucosa has previously been successfully used to repair and functionally augment damaged tissues including, for example, urinary bladder sphincter. Common events to tissue remodeling include widespread and rapid neovascularization, proliferation of granulation mesenchymal cells, biodegradation of implanted submucosal tissue, and lack of immune rejection.
The present invention is directed to the use of vertebrate-derived submucosal matrices as a urinary bladder graft. Submucosal tissue is an inexpensive, nonimmunogenic material that induces host tissue proliferation, remodeling and regeneration of urinary bladder tissues upon implantation. In accordance with this invention tissue graft constructs comprising submucosal tissue of a warm-blooded vertebrate have been found to promote the growth of endogenous urinary bladder tissues having both a urine impermeable cell layer and a function muscle cell layer.
Thus in accordance with the present invention, there is provided a method for reconstructing a diseased or damaged urinary bladder. The method comprises the steps of surgically removing the damaged or diseased portion and replacing the removed portion with a tissue graft construct comprising submucosal tissue of a warm-blooded vertebrate.